The over-arching goal of this proposal is to analyze SARS-CoV-2 antibody seroconversion rates in health care workers at the Emory University Hospital over the next year and to study adaptive immune responses to SARS-CoV-2 infection during acute infection and at convalescence. These studies will draw on three main sources of samples, either through an emerging infectious disease protocol at the Emory Vaccine Center Hope Clinic, through a sero-surveillance study initiated at Emory, and previously collected PBMC and serum samples from adult or elderly donors by Dr. Jorg Goronzy, respectively. We will develop and employ a combination of antibody binding assays and viral neutralization assays to test the quantity and quality of the infection-induced antibody responses. This information will also be used to identify optimal donors for single-cell antibody expression cloning, as we have previously described9-13. A recently purchased 10x instrument in our BSL3 facility at the Emory Vaccine Center will allow for a detailed analysis of the transcriptional profiles of innate and adaptive immune responses during acute SARS-CoV-2 infection. The proposed studies will provide key insight into the dynamics of this devastating disease among health care workers at a major metropolitan hospital in Atlanta. These efforts will also generate key serological tools, provide an understanding of the humoral immune response to SARS-CoV-2 infection, and generate human monoclonal antibodies, with both diagnostic and therapeutic potential.